Phospholipid compounds and methods of making and using the same

Abstract

Phospholipid compounds and methods of using the same, singly or in combination with additional agents, and pharmaceutical formulations of said compounds for the treatment of viral infections are disclosed.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is H, C 3-10  cycloalkyl, C 6-10  aryl, or 5-10 membered heteroaryl containing one, two, or three N; the cycloalkyl, aryl, or heteroaryl of R 1  is optionally substituted with one, two, or three groups independently selected from R 1A  and —NR 13A R 14A ;
 each R 1A  is independently halo, —CN, C 1-3  alkyl, C 1-3  haloalkyl, C 1-3  alkoxy, C 1-3  haloalkoxy, C 3-6  cycloalkyl, or 5-10 membered heteroaryl containing one, two, or three heteroatoms selected from N and O; 
 each R 13A  is independently H or C 1 -C 3  alkyl optionally substituted with NR 13A1 R 14A1 ; R 13A1  is H or C 1-3  alkyl; R 14A1  is H or C 1-3  alkyl; and 
 each R 14A  is independently H or C 1-3  alkyl; 
 
         R 2  is H or C 1-3  alkyl; 
         R 3  is C 1-3  haloalkyl; 
         Q is C 10-21  alkylene or C 10-21  alkenylene; the alkylene or alkenylene of Q is optionally substituted with 1 to 6 Q 1A ; each Q 1A  is independently halo; 
         L is a bond, —O—, or —O(CR 12A R 12B ) n —;
 each R 12A  is independently H or C 1-6  alkyl; 
 each R 12B  is independently H or C 1-6  alkyl; and 
 n is 1 or 2; 
 
         X is a bond or C 1-3  alkylene; 
         T is a bond or —O—; and 
         Z is C 1-6  alkylene; 
         with the proviso that when X is a bond and Tis —O—, then L is a bond. 
       
     
     
         2 - 9 . (canceled) 
     
     
         10 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula Ic: 
       
         
           
           
               
               
           
         
       
     
     
         11 - 13 . (canceled) 
     
     
         14 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein L is —OCH 2 —; and R 2  is H. 
     
     
         15 - 23 . (canceled) 
     
     
         24 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 1  is phenyl optionally substituted with one or two groups independently selected from R 1A , and
 each R 1A  is independently halo, C 1-3  alkoxy, or —CN. 
   
     
     
         25 . (canceled) 
     
     
         26 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is phenyl substituted with F and —CN. 
     
     
         27 - 29 . (canceled) 
     
     
         30 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 -L- is 
       
         
           
           
               
               
           
         
       
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is quinolinyl optionally substituted with one or two groups independently selected from R 1A , and each R 1A  is independently halo, —CN, or C 1-3  alkoxy. 
     
     
         34 . (canceled) 
     
     
         35 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is a bond. 
     
     
         36 . (canceled) 
     
     
         37 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —CH 2 —. 
     
     
         38 . (canceled) 
     
     
         39 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein T is a bond. 
     
     
         40 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Tis —O—. 
     
     
         41 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula Ie: 
       
         
           
           
               
               
           
         
       
     
     
         42 - 44 . (canceled) 
     
     
         45 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q is C 15-20  alkylene, optionally Q is —(CH 2 ) m —, m is 15-20. 
     
     
         46 - 51 . (canceled) 
     
     
         52 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is —CF 3  or —CHF 2 . 
     
     
         53 - 54 . (canceled) 
     
     
         55 . A compound as shown in Table 1, or a pharmaceutically acceptable salt thereof. 
     
     
         56 . A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. 
     
     
         57 - 75 . (canceled) 
     
     
         76 . A compound of  claim 55 , having the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         77 . A compound of  claim 55 , having the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         78 . A compound of  claim 55 , having the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         79 . A compound of  claim 55 , having the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.